In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection
Antimicrobial peptides (AMPs) are alternative therapeutics to traditional antibiotics against bacterial resistance. Our previous work identified an antimicrobial region at the N-terminus of the eosinophil cationic protein (ECP). Following structure-based analysis, a 30mer peptide (ECPep-L) was desig...
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MDPI AG
2022-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/2/386 |
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| author | Jiarui Li Guillem Prats-Ejarque Marc Torrent David Andreu Klaus Brandenburg Pablo Fernández-Millán Ester Boix |
| author_facet | Jiarui Li Guillem Prats-Ejarque Marc Torrent David Andreu Klaus Brandenburg Pablo Fernández-Millán Ester Boix |
| author_sort | Jiarui Li |
| collection | DOAJ |
| description | Antimicrobial peptides (AMPs) are alternative therapeutics to traditional antibiotics against bacterial resistance. Our previous work identified an antimicrobial region at the N-terminus of the eosinophil cationic protein (ECP). Following structure-based analysis, a 30mer peptide (ECPep-L) was designed that combines antimicrobial action against Gram-negative species with lipopolysaccharides (LPS) binding and endotoxin-neutralization activities. Next, analogues that contain non-natural amino acids were designed to increase serum stability. Here, two analogues were selected for in vivo assays: the all-D version (ECPep-D) and the Arg to Orn version that incorporates a D-amino acid at position 2 (ECPep-2D-Orn). The peptide analogues retained high LPS-binding and anti-endotoxin activities. The peptides efficacy was tested in a murine acute infection model of <i>Acinetobacter baumannii</i>. Results highlighted a survival rate above 70% following a 3-day supervision with a single administration of ECPep-D. Moreover, in both ECPep-D and ECPep-2D-Orn peptide-treated groups, clinical symptoms improved significantly and the tissue infection was reduced to equivalent levels to mice treated with colistin, used as a last resort in the clinics. Moreover, treatment drastically reduced serum levels of TNF-α inflammation marker within the first 8 h. The present results support ECP-derived peptides as alternative candidates for the treatment of acute infections caused by Gram-negative bacteria. |
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| language | English |
| last_indexed | 2024-03-09T22:32:13Z |
| publishDate | 2022-02-01 |
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| series | Biomedicines |
| spelling | doaj.art-c093b9f77bc047bf9194d65e0ae8dff82023-11-23T18:54:47ZengMDPI AGBiomedicines2227-90592022-02-0110238610.3390/biomedicines10020386In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> InfectionJiarui Li0Guillem Prats-Ejarque1Marc Torrent2David Andreu3Klaus Brandenburg4Pablo Fernández-Millán5Ester Boix6Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Valles, 08193 Bellaterra, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Valles, 08193 Bellaterra, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Valles, 08193 Bellaterra, SpainBarcelona Biomedical Research Park, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08002 Barcelona, SpainBrandenburg Antiinfektiva GmbH, c/o Forschungszentrum Borstel, 23845 Sülfeld, GermanyDepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Valles, 08193 Bellaterra, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Valles, 08193 Bellaterra, SpainAntimicrobial peptides (AMPs) are alternative therapeutics to traditional antibiotics against bacterial resistance. Our previous work identified an antimicrobial region at the N-terminus of the eosinophil cationic protein (ECP). Following structure-based analysis, a 30mer peptide (ECPep-L) was designed that combines antimicrobial action against Gram-negative species with lipopolysaccharides (LPS) binding and endotoxin-neutralization activities. Next, analogues that contain non-natural amino acids were designed to increase serum stability. Here, two analogues were selected for in vivo assays: the all-D version (ECPep-D) and the Arg to Orn version that incorporates a D-amino acid at position 2 (ECPep-2D-Orn). The peptide analogues retained high LPS-binding and anti-endotoxin activities. The peptides efficacy was tested in a murine acute infection model of <i>Acinetobacter baumannii</i>. Results highlighted a survival rate above 70% following a 3-day supervision with a single administration of ECPep-D. Moreover, in both ECPep-D and ECPep-2D-Orn peptide-treated groups, clinical symptoms improved significantly and the tissue infection was reduced to equivalent levels to mice treated with colistin, used as a last resort in the clinics. Moreover, treatment drastically reduced serum levels of TNF-α inflammation marker within the first 8 h. The present results support ECP-derived peptides as alternative candidates for the treatment of acute infections caused by Gram-negative bacteria.https://www.mdpi.com/2227-9059/10/2/386ECPAMPsinfectionmurine modelGram-negative bacteriaLPS |
| spellingShingle | Jiarui Li Guillem Prats-Ejarque Marc Torrent David Andreu Klaus Brandenburg Pablo Fernández-Millán Ester Boix In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection Biomedicines ECP AMPs infection murine model Gram-negative bacteria LPS |
| title | In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection |
| title_full | In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection |
| title_fullStr | In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection |
| title_full_unstemmed | In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection |
| title_short | In Vivo Evaluation of ECP Peptide Analogues for the Treatment of <i>Acinetobacter baumannii</i> Infection |
| title_sort | in vivo evaluation of ecp peptide analogues for the treatment of i acinetobacter baumannii i infection |
| topic | ECP AMPs infection murine model Gram-negative bacteria LPS |
| url | https://www.mdpi.com/2227-9059/10/2/386 |
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